Vaccine Preventable Diseases

Tetanus, Diphtheria and Pertussis

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Infants and Children
• All infants without contraindications should receive three doses of the child formulation of tetanus-diphtheria-pertussis combination vaccine (abbreviation: DTaP; trade names: Daptacel®, Infanrix®), given at 2, 4, and 6 months of age.
• A fourth dose should be given 6 to 12 months after the third dose, preferably between 15 and 18 months of age.
• A fifth dose is recommended between 4 and 6 years of age.

Adolescents and Adults
• One dose of the tetanus-diphtheria-pertussis booster vaccine (abbreviation: Tdap; trade names: Boostrix®, Adacel®) should be given to all adolescents between the ages of 11 and 18 years.
• Tdap vaccine should also be given to all adolescents and adults who have never previously received it, particularly if they will be in contact with newborn infants in the near future [1-3].

For More Information
• ACIP recommendations: https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/tdap-td.html
• Immunization schedules: http://www.cdc.gov/vaccines/schedules/index.html

Diphtheria disease is mediated by the toxin of the aerobic gram-positive bacterium Corynebacterium diphtheria. The incubation period is generally 2-5 days. Diphtheria can infect almost any mucous membrane, but most commonly infects the pharynx and tonsils. Disease begins insidiously with mild symptoms such as malaise, sore throat, low-grade fever and anorexia. A membrane forms and expands within 2-3 days potentially causing respiratory obstruction, and sometimes results in coma and death within 6-10 days. Complications from diphtheria are mostly attributable to the toxin, and the most common complications other than respiratory obstruction are paralysis and myocarditis.

Tetanus is caused by an exotoxin of the anaerobic gram-positive spore-forming bacterium Clostridium tetani. The spores can survive for years in harsh conditions and are widely distributed in animal feces and soil. The organism generally enters the human body through a cut in the skin at which point the spores germinate and toxins spread through the circulatory and lymphatic systems, interfering with neurotransmitters and leading to muscle contractions and spasms. Incubation averages 8 days but ranges from 3-21 days. The most common type of disease is generalized tetanus, which typically begins with lockjaw and culminates in frequent spasms lasting up to a month. Tetanus is fatal in approximately 11% of cases even when intensive care is available; the disease is twice as likely to be fatal in persons who have never been vaccinated. Neonatal tetanus, although rare in the U.S., can occur when infants are born to mothers who lack tetanus immunity, usually via infection in an unhealed umbilical stump. Because it is an environmental pathogen, there is no community protection (also known as “herd immunity”).

Pertussis, also known as whooping cough, is a highly communicable disease caused by the aerobic gram-negative rod bacterium Bordetella pertussis. The incubation period for pertussis most commonly is 7-10 days. The illness begins with runny nose, sneezing, low-grade fever and mild cough. This cough gradually becomes more severe, progressing into frequent bursts of numerous rapid coughs after 1-2 weeks. These coughing fits (paroxysms) result in the characteristic whooping sound during efforts to inspire. These coughing fits generally continue for 1-6 weeks but can persist up to 10 weeks. Infants are at the highest risk for complications associated with pertussis. The most common complication and cause of most deaths related to pertussis is pneumonia. Pertussis used to be a substantial cause of death in children in the U.S., but since introduction of the vaccine, incidence of pertussis has decreased by more than 80%. However, incidence of pertussis has been gradually increasing again over the past several decades [1].

Acellular pertussis vaccines are inactivated, subunit vaccines, and are only available in combination with diphtheria and tetanus toxoids. DTaP vaccine (trade names: Daptacel®, Infanrix®) is approved for children between six weeks and 7 years of age. Tdap vaccine (trade names: Boostrix®, Adacel®) contains reduced antigen amounts for diphtheria and pertussis, and is approved for persons either 10 through 64 years (Boostrix®) or 11 through 64 years (Adacel®) of age [1].

Vaccine Effectiveness: A complete primary 3 dose series of diphtheria toxoid and tetanus toxoid results in estimated clinical efficacies of 95% and 100%, respectively. The efficacy of the acellular pertussis component of DTaP vaccines licensed in the U.S. has been estimated to be 84% in the short-term (i.e., within 3 years of series completion). The antibody response to one dose of Tdap in adults is similar to that in infants after three doses of DTaP [1, 5, 6]. Infants born to mothers immunized during pregnancy have between 50-100% of the pertussis antibody titers of their mothers [7].

However, immunity wanes over time. By ten years after vaccination, the tetanus antitoxin levels in some individuals decreases below the minimal protective level. Of particular concern is the waning immunity from the acellular pertussis vaccine. This is one of the main reasons for vaccinating with Tdap during every pregnancy [1].

Vaccine Safety: Local reactions including pain, redness and swelling occur in 20-40% of infants after the first three doses of DTaP. Self-limited fever of greater than 101°F occurs in 3-5% of DTaP recipients. Extensive swelling of the injection-site limb and increased local reactions and fever has been reported after the fourth or fifth dose of DTaP. Moderate to severe systemic reactions such as fever above 105°F, febrile seizures, persistent crying lasting longer than 3 hours and hypotonic hyporesponsive episodes occur in less than 1 in 10,000 doses of DTaP [1].

Local reactions occur in 21-66% of adults after Tdap. Fever greater than 100.4°F occurs in 1.4% of Tdap recipients. Mild systemic reactions such as headache or drowsiness occasionally occur after vaccination. Besides very rare occurrences of anaphylaxis, no serious adverse events* have been shown to be caused by Tdap vaccination. Severe allergic reaction (e.g. anaphylaxis) to a previous dose or vaccine component is a contraindication to further Tdap vaccination [1].

Vaccines which may induce fever may also rarely induce febrile seizures. Febrile seizures are a common and typically benign childhood condition, occurring in 2-5% of children at some point during their first five years of life. Febrile seizures have an estimated background incidence of 240–480 per 100,000 person-years in children under five years, although this varies considerably by age, genetics, co-morbidities and environmental risk factors. There are no long-term effects of simple febrile seizures, with the possible exception of an increased risk of recurrence [8-11]. See the Do Vaccines Cause Seizures? summary for more details.

Because syncope has been reported among adolescents receiving vaccinations, adolescent recipients should always receive the vaccine while sitting and not in view of others awaiting vaccination, and be observed for up to 15 minutes immediately after vaccination [12-15].

Contraindications and Precautions: Severe allergic reaction (e.g. anaphylaxis) to a previous dose or vaccine component is a contraindication to further vaccination with DTaP and Tdap. Another contraindication for both vaccines is encephalopathy within 7 days after previous vaccination without an identifiable alternative cause. Current moderate to severe acute illness is a precaution to any vaccination.

Precautions to DTaP include the following occurrences within 48 hours after previous vaccination: a hypotonic hyporesponsive episode, which is a sudden episode of unresponsiveness and limpness [4], a fever above 105°F, or persistent, inconsolable crying lasting over 3 hours. Other precautions include convulsions within 3 days after previous vaccination or an unstable progressive neurologic disorder.

Precautions to Tdap include a history of Guillain-Barré syndrome within 6 weeks after previous vaccination containing tetanus toxoid, or a history of a severe local reaction immediately following previous vaccination containing either tetanus or diphtheria toxoid [1].

Considerations in Pregnancy:
One dose of Tdap is routinely recommended during each pregnancy, preferably between 27 and 36 weeks of gestation.

If a mother is not vaccinated during pregnancy and has never received the Tdap vaccination, the vaccine should be administered to her immediately postpartum [16, 17].

Vaccination with Tdap during pregnancy helps protect infants from pertussis. Newborns and infants in the first few months of life are dependent on transplacentally acquired maternal pertussis antibodies and prevention of exposure from close contacts for protection against pertussis disease, since active immunization of the infant does not begin until 2 months of age and several doses are needed to induce protection against pertussis in most infants. Almost all deaths from pertussis occur in the first few months of life, most prior to receipt of routine infant vaccines against pertussis [16, 17].

Maternal Tdap vaccination was shown to be effective in preventing pertussis disease in infants when used as part of a large-scale vaccination effort in the United Kingdom [18].

A large body of evidence demonstrates the safety of the Tdap vaccine for both pregnant women and their unborn children [16, 17, 19, 20]. Receipt of Tdap during pregnancy is not associated with an increased risk of hypertensive disorders of pregnancy or preterm or small for gestational age (SGA) birth [21]. Having recently received a tetanus-containing vaccination does not increase the risk of adverse outcomes after Tdap vaccination in pregnancy [22]. Concomitant administration of Tdap and influenza vaccines during pregnancy is not associated with a higher risk of adverse outcomes compared to sequential vaccination [23].

* A serious adverse event is defined by the Food and Drug Administration (FDA) as resulting “in any of the following outcomes: Death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.” This definition is found in Title 21, §312.32 of the Electronic Code of Federal Regulations

This summary predominantly relies on the published recommendations from the Advisory Committee on Immunization Practices (ACIP) and the CDC textbook entitled Epidemiology and Prevention of Vaccine-Preventable Diseases, also known as the “Pink Book”. Each summary begins with the recommendations from the ACIP, a committee of 15 experts which advises the Centers for Disease Control and Prevention (CDC) and issues comprehensive statements on the use of individual vaccines, including information on the burden of the disease the vaccine prevents, vaccine effectiveness, vaccine safety, indications, precautions, contraindications, and other critical information. The ACIP individual vaccine recommendations can be accessed at www.cdc.gov/vaccines/hcp/acip-recs/index.html. IVS has complemented the information in many sections with other recent publications. IVS assumes responsibility for the content.

1. Epidemiology and Prevention of Vaccine-Preventable Diseases. In: Hamborsky J KA, Wolfe S ed. 13 ed. Washington D.C.: Centers for Disease Control and Prevention; 2015.
2. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010. MMWR Morb Mortal Wkly Rep. 2011;60(1):13-5.
3. Liang JL, Tiwari T, Moro P, Messonnier NE, Reingold A, Sawyer M, Clark TA. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2018;67(2):1-44.
4. Gold MS. Hypotonic-hyporesponsive episodes following pertussis vaccination: a cause for concern? Drug Saf. 2002;25(2):85-90.
5. Fulton TR, Phadke VK, Orenstein WA, Hinman AR, Johnson WD, Omer SB. Protective Effect of Contemporary Pertussis Vaccines: A Systematic Review and Meta-analysis. Clin Infect Dis. 2016;62(9):1100-10.
6. Zhang L, Prietsch SO, Axelsson I, Halperin SA. Acellular vaccines for preventing whooping cough in children. Cochrane Database Syst Rev. 2014(9):Cd001478.
7. Van Rie A, Wendelboe AM, Englund JA. Role of maternal pertussis antibodies in infants. Pediatr Infect Dis J. 2005;24(5 Suppl):S62-5.
8. (AAP) AAoP. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics. 2011;127(2):389-94.
9. (AAP) AAoP. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008;121(6):1281-6.
10. Bonhoeffer J, Menkes J, Gold MS, de Souza-Brito G, Fisher MC, Halsey N, et al. Generalized convulsive seizure as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation. Vaccine. 2004;22(5-6):557-62.
11. Tse A, Tseng HF, Greene SK, Vellozzi C, Lee GM. Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010-2011. Vaccine. 2012;30(11):2024-31.
12. Kroger 13. Syncope after vaccination--United States, January 2005-July 2007. MMWR Morb Mortal Wkly Rep. 2008;57(17):457-60.
14. Braun MM, Patriarca PA, Ellenberg SS. Syncope after immunization. Arch Pediatr Adolesc Med. 1997;151(3):255-9.
15. Bernard DM, Cooper Robbins SC, McCaffery KJ, Scott CM, Skinner SR. The domino effect: adolescent girls' response to human papillomavirus vaccination. Med J Aust. 2011;194(6):297-300.
16. ACOG Committee Opinion No. 566: Update on immunization and pregnancy: tetanus, diphtheria, and pertussis vaccination. Obstet Gynecol. 2013;121(6):1411-4.General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60(2):1-64.
17. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women--Advisory Committee on Immunization Practices (ACIP), 2012. MMWR Morb Mortal Wkly Rep. 2013;62(7):131-5.
18. Amirthalingam G, Campbell H, Ribeiro S, Fry NK, Ramsay M, Miller E, et al. Sustained Effectiveness of the Maternal Pertussis Immunization Program in England 3 Years Following Introduction. Clin Infect Dis. 2016;63(suppl 4):S236-s43.
19. McMillan M, Clarke M, Parrella A, Fell DB, Amirthalingam G, Marshall HS. Safety of Tetanus, Diphtheria, and Pertussis Vaccination During Pregnancy: A Systematic Review. Obstet Gynecol. 2017;129(3):560-73.
20. Kharbanda EO, Vazquez-Benitez G, Lipkind HS, Klein NP, Cheetham TC, Naleway AL, et al. Maternal Tdap vaccination: Coverage and acute safety outcomes in the vaccine safety datalink, 2007-2013. Vaccine. 2016;34(7):968-73.
21. Kharbanda EO, Vazquez-Benitez G, Lipkind HS, Klein NP, Cheetham TC, Naleway A, et al. Evaluation of the association of maternal pertussis vaccination with obstetric events and birth outcomes. Jama. 2014;312(18):1897-904.
22. Sukumaran L, McCarthy NL, Kharbanda EO, McNeil MM, Naleway AL, Klein NP, et al. Association of Tdap Vaccination With Acute Events and Adverse Birth Outcomes Among Pregnant Women With Prior Tetanus-Containing Immunizations. Jama. 2015;314(15):1581-7.
23. Sukumaran L, McCarthy NL, Kharbanda EO, Weintraub ES, Vazquez-Benitez G, McNeil MM, et al. Safety of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis and Influenza Vaccinations in Pregnancy. Obstet Gynecol. 2015;126(5):1069-74.